During the execution of tests or cultures on biological molecules or cell cultures, plates formed from molded thermoplastic material, e.g. polycarbonate or polystyrene, are usually used today. Usually, the multi-well plate which is used has dimensions of about 80.times.125 mm, and the wells have a diameter of about 8 mm. These dimensions are normalized in industry due to the large variety of apparatuses, which have been developed for automatic analyses. The wells of these plates are often filled with a collection of pipettes, which are displaced manually or by robotized device. The samples of the products formed in the wells are collected, for example with the aid of a collection of needles, of stainless steel or the tips of plastic material, which are immersed in the wells.
Given that it is desirable to carry out a large number of analyses on a single plate, the use of plates having an increasingly large number of wells per plate is growing. An increasingly large number of wells on the same standardized plate gives wells of very small volume, thereby it is then necessary to have tools at one's disposal which enable dispensing small volumes of liquid. Many devices exist for dispensing liquids in small doses ranging from volumes of one milliliter to fractions of a milliliter. Current developments bearing on multi-well plates include progress relating to micro-well and micro-plate technology, it being possible for example to have up to 10,000 wells per square centimeter (see especially U.S. Ser. No. 08/747,425). These wells are separated by a distance of about 100 .mu.m, each well having a depth of 15 to 30 .mu.m and a diameter of 20 to 50 .mu.m. In order to perform tests with the aid of these micro-plates, it is necessary to be able to carry out accurate transfers of liquid volumes ranging from a thousandth to a millionth of a cubic millimeter; transfers to and from such micro-wells. Classical micro-syringes are unable to manipulate such small volumes; thereby it is necessary to make liquid handling apparatuses, which are conceived in a radically novel manner.
A tool is currently on sale, which comprises a matrix of stainless steel pins arranged so that each pin is aligned on a well from a 96-well plate. A drop attaches to an individual pin under the action of the forces of surface tension and can then be transferred. The tool has 30 precision grooves cut into the pins, near to their tip, for determining the volume dispensed. These pins are advertised as capable of dispensing volumes of 1 mm.sup.3 and larger to wells or membrane surfaces.
Micro-syringes use a liquid reservoir comprising a capillary tube (or liquid chamber) and a piston for dispensing the liquid by pushing it out through a needle. Such a system is not suited to the delivery of liquid volumes in the order of a thousandth to a millionth of a cubic millimeter.
It would be desirable to have a method at one's disposal for transferring and dispensing volumes in the order of a thousandth to a millionth of a cubic millimeter into micro-wells of a micro-plate with a good reproducibility. (It is recalled here, in order to facilitate reading the present text, that 1 mm.sup.3 =1 .mu.l=10.sup.-6 l). The invention relates to such a method of transferring and depositing a drop, notably of biological material or of a reagent, onto a surface or into a well or a depression as well as the tool associated with said method.
It would also be desirable to have a method for making a tool for transferring and dispensing volumes in the order of a thousandth to a millionth of a cubic millimeter into micro-wells of a micro-plate. The invention relates to such a method of making a tool for transferring and depositing a drop, notably of biological material or of a reagent, onto a surface or into a well or a depression as well as the tool resulting from the method.